U.S. Pat. Nos. 5,871,010 (xe2x80x9cInhaler Apparatus with Modified Surfaces for Enhanced Release of Dry Powders), U.S. Pat. No. 5,857,456 (xe2x80x9cInhaler Apparatus with an Electronic Means for Enhanced Release of Dry Powdersxe2x80x9d), U.S. Pat. No. 5,753,302 (xe2x80x9cAcoustic Dispenserxe2x80x9d), U.S. Pat. No. 5,788,814 (xe2x80x9cChucks and Methods for Positioning Multiple Objects on a Substratexe2x80x9d), U.S. Pat. No. 5,714,007 (xe2x80x9cApparatus for Electronically Depositing a Medicament Powder Upon Predefined Regions of a Substratexe2x80x9d), U.S. Pat. No. 6,007,630 (xe2x80x9cMethod and Apparatus for Electrostatically Depositing a Medicament Powder Upon Predefined Regions of a Substratexe2x80x9d), U.S. Pat. No. 5,669,973 (xe2x80x9cApparatus for Electrostatically Depositing and Retaining Materials Upon a Substratexe2x80x9d) and U.S. Pat. No. 5,642,727 (xe2x80x9cInhaler Apparatus Using a Tribo-Electric Charging Techniquexe2x80x9d), describe, among other things, the electrostatic deposition of objects, such as particles of powder, on a substrate. The foregoing patent applications are hereby incorporated herein by reference, in their entirety.
The present invention is directed to electrostatic chucks, methods for their use including the electrostatic deposition of particles on an objects, and the objects themselves that have been subjected to electrostatic deposition. In one aspect, the present invention provides an electrostatic chuck for electrostatically attracting an object or objects wherein the object is used in chemical or pharmaceutical assaying or manufacturing. The objects can be pharmaceutical substrates, for example, such as a pharmaceutical tablet or an inhaler substrate.
Additional embodiments of the invention provide chucks and their use to electrostatically attract particles, such as a pharmaceutically active ingredient, to a substrate, such as a tablet. In one aspect, the electrostatic chuck comprises a floating electrode, and is used to selectively attract particles to a substrate above the floating electrode, thereby providing for charge imaging for the deposition of particles in a selected image. Additionally, the invention provides an electrostatic chuck comprising a sensing electrode for sensing the number of particles attracted to the chuck, thereby providing for deposition of an accurate amount of particles. Furthermore, the present invention provides objects having selected areas in which particles are applied to the object via electrostatic means.
In the pharmaceutical industry, pharmaceutical compositions with an active ingredient are prepared by mechanically mixing the active ingredient with pharmaceutically acceptable carriers. A major drawback to this method is the inaccuracy of distribution of the active ingredient in the individual tablets of a batch. This problem is particularly evident when the active ingredient is present in a low dosage, and the inaccuracy of mechanical mixing can result in individual tablets in a single batch having different dosages.
Additionally, for example, some pharmaceutical compositions contain a mixture of various carriers together with the active ingredient in which the carrier is not fully compatible with the active ingredient. For example, the active ingredient may be poorly soluble in the carrier or the carrier may negatively affect the bioavailability of the active ingredient.
These drawbacks of the prior art are addressed by the present invention, in which electrostatic chucks are provided together with their use in the pharmaceutical or chemical industries, providing for accurate deposition of an active ingredient on a tablet, among other advantages.
The disadvantages heretofore associated with the prior art are overcome by inventive technique and apparatus for holding an object or multiple objects, such as tablets, without the use of mechanical force, for deposition of a pharmaceutically active ingredient, for example. The present invention provides advantages including cost-effectiveness, efficiency, and, for example, greater accuracy in the application of a specified pharmaceutical dosage to a pharmaceutical substrate such as a tablet. Further, the deposition of a pharmaceutically active ingredient using static electricity is particularly useful, for example, when the active ingredient is immiscible or otherwise incompatible with the remainder of the tablet or other substrate.
In one aspect, the present invention provides an electrostatic chuck comprising a conductive layer having at least one electrode for electrostatically attracting an object wherein the object is used in chemical or pharmaceutical assaying or manufacturing. For example, the object can be coated with a pharmaceutically active compound. The objects can be numerous types of substrates, including, for example, objects that are suitable for human consumption. The objects can be pharmaceutical substrates, such as an inhaler substrate, a pharmaceutical tablet, capsule, caplet, suppository, dressing, bandage and a patch. In certain embodiments, the pharmaceutical substrate is not dielectric.
Certain embodiments provide the use of an electrostatic chuck to electrostatically attract objects, such as particles, to a recipient substrate. xe2x80x9cParticlesxe2x80x9d are defined herein as objects having a size less than about one millimeter in width or diameter. Thus, the electrostatic chucks of the invention can be used, for example, to attract particles of a powder having a pharmaceutically active ingredient to a recipient pharmaceutical substrate, which substrate may be pharmaceutically inert.
Another aspect of the present invention provides the use of an electrostatic chuck to attract an object wherein the thickness of the object is preferably less than about 5 mm, and more preferably, less 20 than about 3 mm.
In one embodiment of the invention, the electrostatic chuck has two electrodes in the upper conductive layer exposed to the objects, and the two electrodes are preferably interdigitated. In other embodiments, the chuck has a single electrode in the upper conductive layer. The chuck can be used, for example, to hold an object against gravitational forces, or, for example, to position multiple objects on a substrate. See, for example, U.S. Pat. No. 5,788,814.
Certain aspects of the invention provide an electrostatic chuck comprising a floating electrode, wherein the chuck is used to selectively attract objects, such as particles, to a substrate above the floating electrode, thereby providing for charge imaging for the deposition of particles in a selected image. Additionally, the invention provides a sensing electrode for sensing the number of objects, such as particles, that have been deposited onto a recipient substrate. In certain preferred embodiments, a sensing electrode is located on an electrostatic chuck. The sensing electrode provides for deposition of an accurate amount of objects, such as particles. The particles deposited on the recipient substrate can include, for example, a pharmaceutically active ingredient.
Furthermore, the present invention provides objects having selected areas in which particles are applied to the object via electrostatic means.
Additionally, in one aspect, the present invention provides an electrostatic chuck comprising an inhaler substrate, the substrate comprising a conductive layer having at least one electrode for electrostatically attracting particles for inhalation. Preferably, the particles comprise particles of a dry powder comprising a pharmaceutically active ingredient.
The present invention additionally provides methods using an electrostatic chuck. For example, the invention provides a method of chemical or pharmaceutical manufacturing comprising:
(a) providing an electrostatic chuck; and
(b) electrostatically attracting an object to the chuck, wherein the object is used in chemical or pharmaceutical manufacturing.
In addition to a method of manufacturing, the present invention provides the use of an electrostatic chuck to electrostatically attract an object to a substrate wherein the object is a support for a chemical reaction used in a chemical assay or to manufacture chemicals or pharmaceuticals.
The invention also provides the use of an electrostatic chuck to electrostatically attract one object or multiple objects to a substrate wherein the thickness of the object is less than about 3 mm. Additionally, the invention provides for the use of an electrostatic chuck having a bias potential for attracting an object to a substrate, the bias potential being less than the breakdown potential of the materials forming the chuck.
The methods of the present invention can be used with numerous objects including an edible substrate, a pharmaceutical substrate, such as an inhaler substrate, a tablet, capsule, caplet, suppository, dressing, bandage and a patch, and optionally when the substrate is not dielectric. Additionally, the methods of the invention can be used with particles that include a pharmaceutically active ingredient, and the methods of the invention include their use to coat an object, such as a tablet, with a pharmaceutically active compound.
Further, the invention provides a method of attracting a selected number of particles to a substrate, comprising:
(a) providing an electrostatic chuck with a sensing electrode;
(b) applying multiple electrostatically charged particles to the chuck; and
(c) sensing the number of particles attracted to the chuck. This method can be used, for example, with particles of a dry powder wherein the method is used to determine the amount of powder deposited on a substrate attracted to the chuck.
Another aspect of the invention provides a method of depositing particles onto selected areas of a substrate, the method comprising the use of an electrostatic chuck with floating electrodes in areas of the chuck that correspond to the selected areas of the substrate. Additionally, the invention provides a method of manufacturing a pharmaceutical composition comprising (a) providing a pharmaceutical substrate; and (b) electrostatically depositing particles on the substrate, the deposition preferably comprising the use of an electrostatic chuck. Preferably, the electrostatic chuck comprises a floating electrode and the particles are substantially deposited on an area of the substrate corresponding to the floating electrode, and the electrostatic chuck preferably further comprises a sensing electrode for determining the amount of particles deposited on the substrate.
In another aspect, the present invention provides a method for producing a dosage form comprising: (a) providing an electrostatic chuck having an area that is x- or y-addressable; (b) contacting the chuck with objects comprising a pharmaceutically active ingredient, wherein the objects substantially adhere to the chuck in the areas that are x- or y-addressable; and (c) releasing the objects onto a pharmaceutical carrier aligned with the areas of the chuck on which the objects are adhered. Preferably, the chuck has multiple areas that are x- or y-addressable, each area corresponding to a separate pharmaceutical carrier. Further, the objects are preferably substantially simultaneously deposited onto multiple pharmaceutical carriers. This method can be used, for example, to form different dosage units, when at least two of the pharmaceutical carriers receive a different number of objects. This method is particularly convenient for pharmaceutically active ingredients such as hormones that are administered in varying dosages, and it is desirable to form a pharmaceutical package containing more than one type of dosage unit.